Activation of adenylate cyclase by prostaglandin E1 (PGE1), prostacyclin or prostaglandin D2 which leads to the increased level of cellular concentration of cyclic AMP in human blood platelets, is believed to play a critical role not only in normal haemostasis in the coagulation of blood but also in arterial thrombosis by countervailing the platelet aggregation induced by agonists such as ADP, 1-epinephrine, thrombin or collagen. Unlike in the case of purified membrane preparation where PGE1 binds to specific receptor, before adenylate cyclase is activated, the stimulation of the enzymic activity by PGE1 in vivo condition occurs in platelets by transient contact between the cells and the hormone in the absence of the ligand binding. We have recently shown that during the transient contact between the hormone and the platelets a hormonal "memory" is generated in platelets and the increased level of cyclic AMP formation persists even in the absence of PGE1 (Proc. Natl. Acad. Sci. USA, 77:2946, 1980). The proposed research project intends to investigate the mechanism of cyclic AMP formation in the platelet in vivo condition by PGE1 by transient contact and to study the chemical nature of the hormonal "memory" by understanding: 1) the role of guanine nucleotides in the activation f adenylate cyclase in platelets in vivo and in purified membrane preparation; 2) participation of PGE1 receptor and membrane-lipid environment of platelets and 3) the role of phospholipids methylation leading to the activation of adenylate cyclase in the absence of receptor occupancy by PGE1 in platelets. We have also reported that increased cyclic AMP level is associated with the increased synthesis of intra-platelet PGE1 synthesis (Circulation, 62:166, 1980 Abs.). The role of cyclic AMP in PGE1 synthesis and whether PGE1 itself is the "hormonal memory" will be investigated.